Periodontal disease or periodontitis is an inflammatory disease that results in the destruction of both the hard and soft tissues supporting the teeth and has recently been hypothesized as a risk factor for cardiovascular disease. Beck et al. “Dental Infections and atherosclerosis,” American Heart Journal 13:S528–533 (1999). It is estimated that over 10 million people in the United States are currently being treated for the more serious forms of this disease, with approximately 8 billion dollars spent for treatment each year.
Clinically, periodontitis is an inflammation of the periodontium and results in inflammation of the gingiva and may result in resorption of alveolar bone and recession of the gingiva Recession of the gingiva can lead to exposure of the periodontal ligament allowing microorganisms to invade and destroy the ligament.
Infection by a few essential species of bacteria is important in initiating the host inflammatory response that is responsible for the tissue destruction and ultimate loss of teeth. Zambon, J. J., “Periodontal Disease, Microbial Factors,” Ann. Periodontol., 1:879–825 (1996). The major pathogens associated with the disease have been identified and include Porphyromonas gingivalis, Bacteroides forsythus and Actitiobacillus actinomycetemcomitans. Although essential to the pathogenesis, bacteria alone are insufficient to cause the disease. Host factors such as hereditary predisposition and environmental factors such as smoking are believed to equally effect disease occurrence and severity of outcome.
Forms of periodontitis include early onset periodontitis (EOP), chronic adult periodontitis (AP), and refractory periodontitis (RP). Localized juvenile periodontitis is a form of EOP which occurs in otherwise seemingly healthy adolescents and is associated with infection by A. actinomycetemcomitans. “Chronic adult periodontitis” is commonly associated with the presence of B. forsythus, P. gingivalis, many gram-negative asaccharolytic rods, and oral spirochetes. It typically occurs in patients over 35 years of age. Clinically, it resembles acute necrotizing ulcerative gingivitis imposed on rapidly progressive periodontitis. Patients may lose 9 to 12 mm of gingival attachment in as little as six months.
Current treatment for periodontal disease is almost exclusively mechanical and surgical in nature most frequently including scaling and root planing to remove calculus deposits. However, the mechanical treatments do not affect the underlying cause of disease. Antibiotics have also been used as an adjunct therapy, Loesche et al, “Treatment paradigms in periodontal disease”, Compend. Contin. Educ Dental, 18(3):221–6, 228–30 (1997). Unfortunately, results have been disappointing because the antibiotic may not eliminate the bacteria responsible for the inflammatory component, and patients are subject to re-infection.
Accordingly, there is a continuing need for new and effective treatment and preventive measures for periodontal disease. The present invention is directed to this need.